Günaydın Şükran, Kalın Şeyda Nur, Sulukoğlu Emine Karaca, Altay Ahmet, Budak Harun
Science Faculty, Department of Molecular Biology and Genetics, Atatürk University, 25240, Erzurum, Türkiye.
Faculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Kütahya Health Sciences University, 43100, Kütahya, Türkiye.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 11. doi: 10.1007/s00210-025-04363-w.
TrxR1 (Thioredoxin reductase 1) is overexpressed in several types of cancer, containing lung cancer, which is closely linked to metastasis. Hence, TrxR1 has emerged as a target for cancer therapies. In this study, it was aimed to survey whether lecanoric (LA), evernic acid (EA), and vulpinic acid (VA) exert an anticancer effect on lung cancer (A549) cells by targeting the TrxR1 protein. The findings indicated that VA elicited a more notable cytotoxic activity in A549 cells (36.21 µg/mL) at a lower IC value than EA (139.09 µg/mL). Whereas, LA exhibited very low cytotoxic effect in A549 cells. The flow cytometry and qPCR analyses revealed that VA was superior to EA in inducing apoptosis and necrosis in A549 cells. Moreover, the wound healing assay revealed that both EA and VA considerably inhibited the migration of A549 cells. Furthermore, EA and VA markedly decreased protein expression and enzyme activity of TrxR1 in A549 cells. All these findings revealed that EA and VA possess anticancer activities by targeting TrxR1 in A549 cells. Hence, EA and VA can be proposed as candidates for use as a potential chemotherapeutic agent for lung cancer.
硫氧还蛋白还原酶1（TrxR1）在包括肺癌在内的多种癌症中过表达，这与转移密切相关。因此，TrxR1已成为癌症治疗的一个靶点。在本研究中，旨在调查地衣缩酚酸（LA）、扁枝衣酸（EA）和狐衣酸（VA）是否通过靶向TrxR1蛋白对肺癌（A549）细胞发挥抗癌作用。研究结果表明，在较低的半数抑制浓度（IC）下，VA在A549细胞中（36.21μg/mL）比EA（139.09μg/mL）引发了更显著的细胞毒性活性。而LA在A549细胞中表现出非常低的细胞毒性作用。流式细胞术和定量聚合酶链反应（qPCR）分析显示，在诱导A549细胞凋亡和坏死方面，VA优于EA。此外，伤口愈合试验表明，EA和VA均显著抑制A549细胞的迁移。此外，EA和VA显著降低了A549细胞中TrxR1的蛋白表达和酶活性。所有这些发现表明，EA和VA通过靶向A549细胞中的TrxR1具有抗癌活性。因此，EA和VA可被提议作为肺癌潜在化疗药物的候选物。
